Department of Gastroenterology, Tianjin Medical University General Hospital, Tianjin, China.
Department of Gastroenterology, The Third Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
Cell Transplant. 2021 Jan-Dec;30:9636897211008874. doi: 10.1177/09636897211008874.
CircRNAs participate in the pathogenesis of a variety of cancers. Previous studies showed that baculoviral IAP repeat containing 5 (BIRC5) can promote tumor progression. But, the mechanisms by which circRNAs regulate BIRC5 expression in hepatocellular carcinoma (HCC) remain unknown. The clinical prognosis of BIRC5 or miR-497-5p expression in patients with HCC was assessed by TCGA RNA-seq dataset. hsa_circ_0026939 (circANKRD52) or BIRC5 was identified to bind with miR-497-5p by luciferase gene report, RIP and circRIP assays. MTT, colony formation, Transwell assays and a xenograft tumor model were used to estimate the role of miR-497-5p or circANKRD52 in HCC cells. As a result, we found that elevated expression of BIRC5 or decreased expression of miR-497-5p was linked to poor survival in HCC. Restored expression of miR-497-5p repressed cell proliferation, colony formation and invasiveness by targeting BIRC5, but its inhibitor showed the opposite results. Furthermore, circANKRD52 possessed a tumor-promoting effect by acting as a sponge of miR-497-5p and thereby upregulated BIRC5 in HCC cells. In conclusion, our findings demonstrated that circANKRD52 enhances the tumorigenesis of HCC by sponging miR-497-5p and upregulating BIRC5 expression.
circRNAs 参与多种癌症的发病机制。先前的研究表明杆状病毒 IAP 重复序列 5(BIRC5)可以促进肿瘤进展。但是,circRNAs 调节 HCC 中 BIRC5 表达的机制尚不清楚。通过 TCGA RNA-seq 数据集评估了 BIRC5 或 miR-497-5p 在 HCC 患者中的临床预后。通过荧光素酶基因报告、RIP 和 circRIP 测定鉴定 hsa_circ_0026939(circANKRD52)或 BIRC5 与 miR-497-5p 结合。MTT、集落形成、Transwell 测定和异种移植肿瘤模型用于评估 miR-497-5p 或 circANKRD52 在 HCC 细胞中的作用。结果发现,BIRC5 表达升高或 miR-497-5p 表达降低与 HCC 患者的不良生存相关。miR-497-5p 的恢复表达通过靶向 BIRC5 抑制细胞增殖、集落形成和侵袭性,但其抑制剂则表现出相反的结果。此外,circANKRD52 通过充当 miR-497-5p 的海绵并上调 HCC 细胞中的 BIRC5,发挥促肿瘤作用。总之,我们的研究结果表明,circANKRD52 通过海绵 miR-497-5p 和上调 BIRC5 表达增强 HCC 的肿瘤发生。